Analysis of biologically-active, endogenous carboxylic acids based on chromatography-mass spectrometry

•Analysis of fatty acids, eicosanoids, small carboxylic acids and bile acids.•We explain the pitfalls and the advantages of LC-MS and GC-MS platforms.•Overview of recent derivatization strategies in analysis of carboxylic acids.•We describe the biological relevance and the need for advanced analysis platforms.

Carboxylic acids (CAs), such as small CAs, fatty acids, eicosanoids and bile acids, are involved in numerous biological processes. Mapping the participating pathways potentially yields great insight into the physiological state of an organism. There is demand for analytical techniques that are more sensitive, faster and easier to handle. These would enable advanced analysis and validation in larger clinical cohorts and hopefully deliver useful disease markers. The analysis of CAs is not only driven by the CA group, but also largely dependent on chain length and other functional groups present. Several liquid and gas chromatography strategies, with or without derivatization, were developed in recent years. Here, we review the most recent trends in analysis of endogenous CAs by chromatography-mass spectrometry. We critically evaluate sample preparation, derivatization techniques, separation and mass spectrometric detection. Ultimately, the reader is guided to the most versatile, sensitive and easy analytical methods.